A Longitudinal Follow-Up of 550 Mild Cognitive Impairment Patients: Evidence for Large Conversion to Dementia Rates and Detection of Major Risk Factors Involved

Article type: Research Article

Authors: Espinosa, Ana^a | Alegret, Montserrat^{a; *} | Valero, Sergi^{a; b} | Vinyes-Junqué, Georgina^a | Hernández, Isabel^a | Mauleón, Ana^a | Rosende-Roca, Maitée^a | Ruiz, Agustín^a | López, Oscar^{c; d; e} | Tárraga, Lluís^a | Boada, Mercè^{a; f}

Affiliations: [a] Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain | [b] Psychiatry Department, Hospital Universitari Vall d'Hebron, CIBERSAM, Universitat Autònoma de Barcelona, Spain | [c] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA | [d] Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA | [e] Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA | [f] Hospital Universitari Vall d'Hebron -Institut de Recerca, Universitat Autònoma de Barcelona (VHIR-UAB), Spain

Correspondence: [*] Correspondence to: Montserrat Alegret, Fundació ACE, Institut Català de Neurociències Aplicades, C/Marquès de Sentmenat, 35-37, 08014 Barcelona, Spain. Tel.: +34 93 4304720; Fax: +34 93 4193542; E-mail: [email protected].

Abstract: The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimer's disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersen's criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could explain cognitive deficits. MCI cases were divided into Probable amnestic (Pr-aMCI) (n = 115), probable non-amnestic (Pr-naMCI) (n = 37), possible amnestic (Pss-aMCI) (n = 234), and possible non-amnestic (Pss-naMCI) (n = 164), single or multiple domain. In the whole MCI sample, regression analysis showed that low performances on Orientation, Verbal Delayed Recall of the Word List Learning test from WMS-III, and Luria's Clock test were associated with conversion to dementia, independently of APOE ε4 allele. Cox proportional-hazards showed that the Probable MCI subtype, presence of storage memory impairment, multiple domain condition, and presence of at least one ε4 allele increased the risk of conversion to dementia. Multivariate survival and Kapplan-Meier analyses showed that the Pr-aMCI with storage memory impairment had the most and closest risk of conversion to dementia. In conclusion, the Pr-aMCI subset of patients had 8.5 times more risk of converting to dementia than the Pss-naMCI group, who displayed the slowest conversion rate to dementia.

Keywords: Amnestic, cognition, dementia conversion, genetics, mild cognitive impairment, risk factors

DOI: 10.3233/JAD-122002

Journal: Journal of Alzheimer's Disease, vol. 34, no. 3, pp. 769-780, 2013